Advanced optical microscopic techniques recently developed in our laboratory have permitted visualization in great detail the morphologic features of human platelet transformation which are otherwise clearly observable only by electron microscopy. During the half hour required for a single experiment such processes as pseudopod extension and retraction, spreading, and degranulation can be directly observed in living platelets as continuous events which can be recorded on cine film. In addition, the rates at which these changes occur can be quantified in statistical populations of platelets. The phenomena observed are those least susceptible to direct study by other tests of platelet function. By comparing results obtained by optical microscopy (differential interference contrast, surface interference reflection, single sideband) with scanning and both conventional and high voltage transmission electron microscopy, freeze fracture techniques, biochemical analyses, platelet aggregometry, etc.; much stands to be learned about the roll of the platelet in normal and abnormal hemostasis and thrombosis. The new high resolution optical techniques (together with conventional techniques will be applied to: 1) the study of basic mechanisms of platelet motile reactivity; 2) the study of the dynamics of the platelet-fibrin interaction (e.g., clot retraction); and 3) the study of the biologic variability of platelet forms by direct observation of unfixed specimens. Data obtained in studies of normal platelets will serve as a basis for comparison with data from individuals with hereditary platelet diseases and to platelets under the influence of drugs which are either proven or suspected of being therapeutically efficacious in preventing thrombosis (e.g., heart attack and stroke). These studies will be facilitated by the development of automated and semi-automated data processing techniques.